A genetic mutation that a Chinese scientist tried to create in twin girls born last year, in the hope of protecting them against HIV, has been found to raise the risk of an early death.
He Jiankui at the Southern University of Science and Technology in Shenzhen sparked an international outcry in November when he announced the birth of twin girls, Lulu and Nana, after he edited the DNA in their embryos.
The procedure was meant to mimic a natural mutation that protects about 10% of northern Europeans from HIV infection. But in new research, scientists in the US found that the mutation is linked to shorter life expectancy. By the age of 74, the death rate was on average 26% higher in Britons who carried mutations in both copies of the gene, compared with those who had mutations in only one copy or neither.
He targeted a gene called CCR5 which makes a protein that protrudes from the surface of immune cells. While scientists are unclear exactly what the CCR5 protein does, the HIV virus latches on to it to enter and infect cells. A natural mutation called delta 32 disables the protein and so prevents HIV from getting inside cells.
While He failed to replicate the natural mutation, he instead appeared to introduce different mutations which disabled a single copy of the CCR5 gene in one of the girls, and both copies of the gene in the other.
A preliminary Chinese government investigation released in January found that in performing what is called germline genome editing, where genetic changes are made that can be passed on from generation to generation, He had sidestepped regulations and oversight and had used fake ethical review documents in pursuit of “personal fame”. In editing the DNA of the babies, the scientist had claimed an infamous world first.
To investigate the impact of disabling the CCR5 gene, Xinzhu “April” Wei and Rasmus Nielsen at the University of California in Berkeley analysed medical records linked to the genomes of more than 400,000 people registered with the UK Biobank. Among 41- to 78-year-olds, the death rate was on average 21% higher in people who carried delta 32 mutations in both copies of the CCR5 gene, compared with those who had mutations in only one copy or none. Everyone inherits two copies of the gene, one from each parent.
It is unclear how CCR5 mutations affect lifespan but previous research has suggested that they make it more likely for people to die from the flu. “In this case, the cost of resistance to HIV may be increased susceptibility to other, and perhaps more common, diseases,” the authors write in Nature Medicine.
Adrian Hill, professor of human genetics at Oxford University, who was not on the research team, said the work stressed how important it was for scientists to understand the full impact that genetic changes might have on people. “It begs the question that if we start making other genetic changes that are clearly functional, do we really know what’s going to happen in later life?”
Robin Lovell-Badge, a geneticist at the Francis Crick Institute in London, added: “This really shows that if you’re going to do germline genome editing, you really need to understand what the gene is that you’re editing and what it does in detail. And it emphasises that CCR5 was a terrible choice because we don’t know enough about the normal role of the gene.”
Jonathan Ball, a professor of molecular virology at the University of Nottingham, who also was not involved in the research, said the work showed how germline editing can have potential impacts that go beyond the intended consequences of those edits.
“In the case of the infamous gene-edited Chinese babies, the intention was to create babies that were highly resistant to HIV infection. However, the current study would suggest that in doing so, the scientist responsible for their creation might have also reduced their life expectancy,” Balll said. “Undoubtedly gene editing can be a force for good, but there has to be a thorough analysis of both intended and unintended consequences as part of any approval process.”